Soil-dwelling bacteria of the genus Frankia
have the potential to produce a multitude of natural products,
including antibiotics, herbicides, pigments, anticancer agents, and
other useful products, according to Bradley S. Moore of the Scripps
Oceanographic Institute, La Jolla, and his collaborators in an article
in the June 2011 issue of the journal Applied and Environmental Microbiology.

The researchers found
genetic structures in this bacterium that resemble those of various
valuable natural product categories through bioinformatics and genome
mining. “This tremendous biosynthetic capacity is reminiscent of many
industrially important bacteria such as those belonging to the genus, Streptomyces that produce the majority of the natural antibiotics used as drugs,” says Moore.

“To see this capacity
in a well-known microbe not previously exploited for its chemical
richness was very rewarding from both an applied and basic science
point of view,” says Moore. Frankia are nitrogen-fixing
bacteria that live in symbiosis with actinorhizal plants (whose ranks
include beech and cherry trees, and various gourd-producing plants).
“Since the vast majority of the deduced [biosynthetic] pathways are
unique to Frankia, it suggests that they employ a very
complex and specialized communication with their plant host to
establish and maintain their symbiosis. So lots to discover there.”

Frankia have
not previously been exploited partly because these bacteria are
difficult to grow in the lab. But new genetic methods make it easier to
transplant genes for promising natural products from Frankia into “more user-friendly host bacteria for production,” says Moore.

Moreover, genome
mining, a recent technique that involves searching for genetic
sequences, was critical to the results, and “complementary to the far
more laborious traditional natural product drug discovery that has gone
unchanged for decades,” says Moore. A greater understanding of how
complex organic molecules are synthesized in nature laid additional
groundwork for this, and for “a new revolution in the discovery of
natural chemicals that will fuel new research into what functions these
chemicals play in nature, and how they can be used to benefit society,”
says Moore.

The project grew out of
a graduate class that Moore and Daniel Udwary (then his post-doc, now
at the University of Rhode Island) taught on “Microbial Genome Mining,”
says Moore. Each student in the class researched a group of
biosynthetic gene clusters that Moore and Udwary preselected. The
students—who are the majority of coauthors on the paper—annotated their
genes and based on biosynthetic principles, and predicted pathways
leading to putative natural products. They then worked with the
laboratories of Pieter Dorrestein at the University of California, San
Diego (a mass spec specialist) and Lou Tisa at the University of New
Hampshire (a Frankia biologist) to conduct preliminary
proteomic and metabolomic analyses to probe whether the predicted
pathways were operative, and whether small molecule chemistry was
evident.